The Role of Immobilized Phospholipids in the Initiation of Blood Coagulation under Flow Conditions

Abstract

Localized thrombin production appears to be a key event in the hemostatic response to the vascular injury. This protein causes irreversible activation of platelets and is responsible for the formation of a fibrin mesh that stabilizes the hemostatic plug. It is generally accepted that flow has a strong inhibitory effect on the kinetics of plasma coagulation reactions, so that thrombin generation and fibrin formation are restricted to the areas, which are protected from the diluting effect of the blood flow, for example, inside the platelet aggregate or in the subendothelial matrix. However, experimental evidence indicates the possibility of in vitro fibrin polymerization at arterial shear rates in the absence of platelets. Here, using in vitro experiments and in silico models, we show that the initiation of plasma coagulation under arterial shear rates can occur due to the presence of an immobilized phospholipid fraction in the area mimicking the damaged vascular wall. Our results suggest that binding of coagulation factors to these phospholipids allows the initial stages of plasma coagulation to be protected from the flow and leads to a rapid thrombin production even under conditions of arterial blood shear rates. Thus, the obtained data suggest that under certain conditions activation of secondary hemostasis may precede and promote platelet activation and aggregation.